Anti-vaccine protesters tear down NYC COVID-19 testing site

 A group of people demonstrating against the coronavirus vaccine tore down a COVID-19 testing site in New York City during a protest Monday. 

Hundreds of demonstrators gathered to protest the coronavirus vaccine mandate for public school employees, according to a report from The Washington Post. 

According to a mandate issued by New York City Mayor Bill de Blasio (D), Monday marked the deadline for employees to receive at least one dose of the coronavirus vaccine or be forced to accept unpaid leave.

Protesters marched in Brooklyn and Manhattan, chanting slogans through loud speakers such as "let us teach!" and "We the people will not comply," according to the Post. 

The protesters tore down a COVID-19 testing site and confronted a worker at the site, according to the paper. However, police said that there were no mass arrests on Tuesday. 

De Blasio (D) said 95 percent of employees have complied with the vaccine mandate on Monday.

“Look, here’s my message to all of the mayors of America, here’s my message to all of the governors of America: Put these mandates in place. Put these incentives in place,” he said. “They work. Do it now. Save lives and ultimately save this country from a longer crisis that could hold us down for months or even years.”

Vaccine mandates have been put in place all around the country in businesses and schools, and President Biden announced a new rule last month to be issued through the Occupational Safety and Health Administration that would require all businesses with 100 employees or more to mandate vaccines or frequent testing. 

New York City also has some of the strictest mitigation measures — people have to present a COVID-19 vaccination card to enter restaurants. 

Despite protests against the mandates, many companies implemented them after the Pfizer vaccine was fully approved by the Food and Drug Administration. 

https://thehill.com/homenews/state-watch/575379-anti-vaccine-protesters-tear-down-covid-19-testing-site-in-new-york-city

Synaptogenix: Rebuilding Connections, Fostering Growth

 How well we think, feel and act rests in the hands of trillions of tiny connectors in our minds.

Synapses play an integral role in how we function; they are tiny gaps that allow neurons to communicate with each other. When they aren’t working correctly or are damaged, it can lead to less connectivity, a weaker nervous system, and impaired cognition in the brain. It’s no surprise that loss of these synapses can lead to major neurological diseases like Alzheimer’s disease and dementia that interfere with a person’s ability to operate independently. 

Nearly 1 in 6 people around the world suffer from neurological diseases each year, and unfortunately, there are limited treatment options are available. Thanks to the clinical-stage biotech company Synaptogenix 

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Getting the Brain Back On Track

Its product, Bryostatin-1, activates the protein kinase C-epsilon (PKC-epsilon), which affects the cognitive function of the patient as it promotes both neuronal health and synaptic regeneration. Unlike similar products made by Athira Pharma 

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, Synaptogenix’s product directly affects the PKC-epsilon - synaptic growth pathways, showing improvement. Not only has the drug slowed cognitive decline in those with Alzheimer’s disease, it has actually improved cognitive function past baseline with the effect showing persistence after 1 month of dosing.

In its Phase 2 pilot for Alzheimer’s disease, Bryostatin-1 has also reported no safety issues and has been administered safely in over 1,600 patients. Aside from Alzheimer’s disease, the company is also looking at indications for other diseases and disorders like Fragile X syndrome, autism, multiple sclerosis, Parkinson’s disease, traumatic brain injury and stroke. 

A Brighter Future Ahead

Valued at $30 million and led by a management team that has over 30 years in the field of neurodevelopmental disorders and developing novel drugs, Synaptogenix has received over $200 million of funding from Blanchette Rockefeller Neurosciences Institute and the National Institutes of Health (NIH) for further studies. In addition, it has numerous well-known partnerships, including the NIH, National Cancer Institute and National Institute on Aging.

Recently, Synaptogenix has made news by signing a memorandum of understanding with Nemours A.I. DuPont Hospital for Children to initiate trials using Bryostatin to treat Fragile X syndrome, announcing positive results from its Alzheimer’s trial, and acquiring a regenerative patent award with the U.S. Patent and Trademark Office. These patents could apply to treating degeneration of brain wiring in other neurological disorders such as Multiple Sclerosis, Fragile X mental retardation, Parkinson's disease, and cerebrovascular dementia.

https://www.benzinga.com/general/biotech/21/10/23214212/rebuilding-connections-fostering-growth-synaptogenix-could-be-a-beacon-of-hope-for-patients-with-

State With Highest Vax Rate Sees Record Surge In COVID Cases

 by Ivan Pentchoukov via The Epoch Times,

Vermont, the state with the highest vaccination rate in the United States, is experiencing a CCP virus surge at levels not seen since the pandemic’s peak last winter.

The number of cases in Vermont is at a record level, hospitalizations are close to the records notched last winter, and the state recorded the deadliest day and the second deadliest month of the pandemic in September.

“I think it’s clearly frustrating for all of us,” Michael Pieciak, the commissioner of the Vermont Department of Financial Regulation who monitors CCP (Chinese Communist Party) virus statistics for the state.

More than 69 percent of Vermont’s population has been fully vaccinated against COVID-19 as of Sept. 24, according to the CDC, far above the national rate of 56 percent.

The state recorded the highest rate of hospitalizations per 100,000 residents on Sept. 30, breaching a record set on Jan. 31 last year. Eight people died of the CCP virus in Vermont on Sept. 13, the highest grim total recorded since the outbreak of the virus.

In late August, four of ten cases of COVID-19 in Vermont were among vaccinated people, according to a letter signed by 90 employees of the Vermont Health Department, including state Epidemiologist Patsy Kelso.

Gov. Phil Scott (R) lifted the state of emergency in Vermont in June when 80 percent of the population had received at least one shot of the vaccine. He has since indicated he is wary of reimposing the state of emergency.

“We can’t be in a perpetual state of emergency,” Scott said this week.

The four states which follow Vermont in terms of the highest vaccination rates in the nation are also experiencing alarming signs.

The head of UMass Memorial Health, the largest health system in central Massachusetts, said recently that regional hospitals were seeing nearly 20 times more COVID-19 patients than in June and there isn’t an ICU bed to spare. Massachusetts has the fifth-highest vaccination rate in the nation.

In Connecticut, the second most vaccinated state in the U.S., the legislature recently extended the governor’s emergency powers to make it easier to cope with the latest wave of the pandemic.

On Sept. 22, Maine, the third most-vaccinated U.S. state, had nearly 90 people in intensive care units, a pandemic peak for the state.

https://www.zerohedge.com/covid-19/not-supposed-happen-us-state-highest-vaxx-rate-sees-record-surge-covid-cases

Merck preps filings for oral COVID drug, but is it really a game changer?

 Merck & Co is on the brink of plugging a gap in the coronavirus treatment armamentarium after its oral drug molnupiravir cut deaths and hospitalisations in mild or moderate COVID-19 in a phase 3 trial.

Merck and partner Ridgeback Therapeutics have said they will see emergency use authorisation from the FDA for molnupiravir on the strength of the data, which suggest the drug could be used in the community to keep people from developing severe COVID-19.

At the moment drugs like dexamethasone and Gilead Sciences’ intravenous antiviral Veklury (remdesivir) can be used in hospitals to reduce mortality in severe COVID-19.

Antibody therapies meanwhile have been developed for non-hospitalised patients, but these still have to be administered by infusion in a clinic.

A treatment that could be given to patients at home that would prevent them developing more severe symptoms could save lives and reduce the burden on hospitals during the crisis, according to Wendy Holman, Ridgeback’s chief executive.

Like Veklury, molnupiravir is a polymerase inhibitor that blocks the replication of the SARS-CoV-2 virus, and has been shown in lab studies to target other respiratory viruses like influenza and Ebola.

The results of the MOVe-OUT trial in people with mild or moderate COVID-19 show a significant 50% reduced risk of hospitalisation or death at a planned interim analysis for molnupiravir compared to placebo, cutting the actual risk to 7% from 14% 29 days after the start of dosing.

The trial is fairly small with fewer than 400 subjects per arm, so the numbers involved are low, but Merck and Ridgeback have reported zero deaths with molnupiravir versus eight deaths in the placebo group at that timepoint.

It was carried out in people at higher risk of progressing to more severe COVID-19, including those who are older or have other health problems like obesity, diabetes and heart disease.

An earlier trial of molnupiravir in severe COVID-19 called MOVe-IN was stopped in April on the grounds there was insufficient clinical benefit with the drug. The different outcomes suggest the drug is more effective when administered in the earlier stages of infection.

One commentator welcomed the positive outcome in MOVe-OUT, but cautioned against getting “carried away” by the results.

“It’s worth remembering that…dexamethasone was found to save around a third of people who would have died with severe COVID-19, but its clinical introduction did not prevent nearly 100,000 deaths in the UK in the past 12 months,” said Dr Simon Clarke, associate professor in cellular microbiology at the University of Reading.

There still isn’t much data available on the side effects of molnupiravir, he added, and subjects in the trial were instructed to abstain from heterosexual sex or use contraception, which might point to a risk of birth defects.

Prof Peter Horby, an infectious disease specialist at the University of Oxford, has also sounded a note of caution, as the data suggests that “quite a lot of people need to be treated to prevent one hospitalisation or death,” and that means “the drug needs to be very safe and affordable.”

Merck already has a supply deal in place for molnupiravir with the US government, which has agreed a $1.2 billion order for 1.7 million doses at a price of $700 per course, as well as deals with other countries around the world, pending regulatory approvals.

The company said it expects to produce 10 million courses of treatment by the end of 2021, with more doses coming in 2022 pending regulatory approvals. It has also signed licensing deals with drugmakers in India to make the drug available more widely in low- and middle-income countries.

The big challenge will be to target the drug effectively, and intervening with it early enough in the course of infection to have an impact on the virus. In the MOVe-IN trial, all subjects were within five days of symptom onset, which may be more challenging to achieve in the community.

According to Dr Peter English, immediate past chair of the BMA Public Health Medicine Committee, quite a lot of the people who develop severe COVID-19 don’t have any significant risk factors.

“Unless an antiviral medication could be made so cheap and so safe that it can be used ‘on spec’ by people who might have COVID-19, they are unlikely to be widely useful,” he remarked.

https://pharmaphorum.com/news/merck-preps-filings-for-oral-covid-drug-but-is-it-really-a-game-changer/

Merck's molnupiravir seen 'complementary, but not a competitor' to COVID-19 vaccines

 What do Merck’s eye-opening data, recently released for its antiviral molnupiravir on high-risk COVID-19 patients, mean for manufacturers of vaccines?

Analysts from the ODDO BHF financial services group see little impact in the short and intermediate term. Even though inoculation rates are low in most lesser developed countries, ODDO says it’s unlikely that countries will shift away from vaccination campaigns to focus primarily on treating high-risk patients with COVID.

This is the case despite trial data showing molnupiravir providing a 50% reduction in the hospitalization rate and a 100% reduction in the death rate among patients within five days of symptomatic illness.  

“The impact on vaccine manufacturers such as Moderna should be limited,” ODDO wrote in a report to investors. “We believe that molnupiravir can be complementary to the COVID-19 vaccine but not a competitor.”

With Merck able to manufacture no more than 10 million doses of the oral treatment the rest of this year, far less than what is needed worldwide, there should be little change in demand for vaccine, ODDO said. Additionally, the analysts don’t see a significant change in the number of patients hospitalized because of the emergence of molnupiravir.

Many factors will continue to fuel demand for vaccines, ODDO says, citing new orders, booster shot rollouts, the push to vaccinate children and the need for new multivalent vaccines as new variants spread.

“Momentum should continue to build in 2022,” ODDO wrote.

As for Merck, the data put molnupiravir in a position to become the standard of care for high-risk COVID-19 patients, Bernstein analysts said.

This represents a “significant win,” for Merck, analyst Ronny Gal wrote. “But the 8.4% stock move seems to capture a generous scenario.”

They figure that the treatment will be approved by the end of this year, but the market may soon be crowded, as other antivirals, made by Pfizer and Roche, are in late-stage testing. Based on molnupiravir’s study results, Bernstein expects these companies will also present strong data and be close behind with approvals.

So how much revenue will Merck generate from molnupiravir?

Bernstein took a stab at a figure for 2022 based on an estimate that 20 million Americans—roughly the same as this year—will be infected and 20% of them will be treated with oral antivirals. Based on Merck’s price of $700 per dose, per a recent supply deal with the U.S. government, Bernstein sees potential for $2.8 billion in sales in the U.S. and $5 billion worldwide.   

There’s another factor that bodes well for the future of antivirals as COVID treatments, Bernstein analysts say. In general, antivirals offer greater hope against variants because they “target proteins other than spike,” Gal wrote.

https://www.fiercepharma.com/pharma/merck-s-molnupiravir-will-be-complementary-but-not-a-competitor-to-covid-19-vaccines-analyst

Astrazeneca tries its luck in Covid-19 prevention

 Astrazeneca’s filing for emergency use of AZD7442 for Covid-19 prevention looks like an attempt to steal a march on Regeneron and Lilly’s already authorised MAbs. Whether it will succeed is a separate question. Astra says “AZD7442 (could) be the first long-acting MAb to receive an EUA for Covid-19 prevention”, though Regeneron’s Regen-Cov and Lilly’s bamlanivimab/etesevimab, both normal-acting, already have EUAs for post-exposure prophylaxis in subjects at high risk of severe Covid-19. Astra’s application appears to seek a broad EUA for Covid-19 prevention, even though only its pre-exposure study, Provent, succeeded; Storm Chaser, for post-exposure prophylaxis, failed. A separate question for the FDA will be whether to authorise AZD7442 in vaccinated as well as unvaccinated people; the Regeneron and Lilly prophylaxis EUAs are for unvaccinated people and those who are vaccinated but unable to mount a strong immune response, but Astra’s trials were specifically in the unvaccinated population. A similar consideration exists for Merck & Co’s oral antiviral molnupiravir, which last week scored in a Covid-19 treatment study in unvaccinated people. While it might seem unethical to deny a drug based on patients’ vaccination status, reimbursement for molnupiravir might be justifiable only in its specific studied population.

Selected antivirals & MAbs for treating Covid-19
Project	Company	Setting	Trial	Vaccinated people allowed?
Molnupiravir	Merck & Co/Ridgeback	Outpatient treatment	Move-Out, succeeded	No*
		Post-exposure prophylaxis	Move-Ahead, data H1 2022	No
AT-527	Roche/Atea	Outpatient treatment	Morningsky, ends Nov 2021	Yes if vaccinated >40 days previously
PF-07321332	Pfizer	Low-risk outpatient treatment	NCT05011513, ends Oct 2021	No, except those with underlying condition
		High-risk outpatient treatment	NCT04960202, ends Nov 2021	No
		Post-exposure prophylaxis	NCT05047601, data H1 2022	No
Favipiravir	Appili	Outpatient treatment	Preseco, ends Sep 2021	Yes
RHB-107 (upamostat)	Redhill Biopharma	Outpatient	NCT04723537, ends Sep 2022	Yes
AZD7442	Astrazeneca	Post-exposure prophylaxis	Storm Chaser, failed	No
		Pre-exposure prophylaxis	Provent, succeeded	No
		Outpatient treatment	Tackle, data H2 2021	No
Regen-Cov (casirivimab + imdevimab)	Regeneron	Treatment (has EUA)	COV-20678	No
		Post-exposure prophylaxis (has EUA**)	COV-2069	Yes
Bamlanivimab + etesevimab	Lilly/Abcellera	Treatment (has EUA)	Blaze-4	Yes, except low-risk individuals
		Post-exposure prophylaxis (has EUA**)	Blaze-2, part 1	No
Source: Evaluate Pharma & clinicaltrials.gov. Notes: *per Wolfe Research, not specified on clinicaltrials.gov; **in unvaccinated people, or vaccinated people unable to mount strong immune response. https://www.evaluate.com/vantage/articles/news/snippets/astrazeneca-tries-its-luck-covid-19-prevention

Vedanta makes Clostridioides difficile look easy

 Microbiome-targeting agents seem to have a decent shot at treating C difficile infections, if they are rather less certain in other settings. Vedanta said today that its pill VE303, a combination of eight strains of live bacteria grown in cell banks, achieved a 31.7 percentage point risk reduction versus placebo in the rate of infection recurrence. The data refer to only the higher dose administered in the phase 2 Consortium trial; on the lower dose Vedanta is silent. Still, the data were good enough to spur Barda to hand over $23.8m to support phase 3 studies, under a contract it has had with Vedanta since last year. These trials ought to begin next year, putting Vedanta some way behind Seres and Ferring. The former hopes to file its C diff project SER-109 for US approval next year, and Ferring should get its pivotal data in the same time frame. Elsewhere, Kaleido Biosciences reported topline biomarker data from a tiny trial of its microbiome asset KB295 in mild-to-moderate ulcerative colitis. A phase 2 trial is slated for 2022, and the group will hope to avoid the dismal fate of Seres in this disease. 

Data from the Consortium trial of Vedanta's VE303
	High-dose VE303	Placebo
Recurrence rate within 8wk	13.8%	45.5%
Reduction vs placebo in the odds of a recurrence	81%, p=0.0077
Source: company release. https://www.evaluate.com/vantage/articles/news/snippets/vedanta-makes-clostridioides-difficile-look-easy